Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance

Zhou, Junying; Lei, Ningjing; Tian, Wanjia; Guo, Ruixia; Chen, Mengyu; Qiu, Luojie; Wu, Fengling; Li, Yong; Chang, Lei

doi:10.3389/fonc.2022.999643

Cited by 9 publications

(12 citation statements)

References 169 publications

(191 reference statements)

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“…Tumor formation and antitumor immunity are strongly influenced by the TME, which encompasses a variety of immunological and stromal cell types. 84 MRGs and TME immune cell infiltration have been linked in previous stusies. 72,85 We also observed various MRG-lncRNA-related TME cell-infiltrating properties throughout our experiment.…”

Section: Discussionmentioning

confidence: 96%

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An m1A/m6A/m5C‐associated long non‐coding RNA signature: Prognostic and immunotherapeutic insights into cervical cancer

Pan,

Lin,

Dai

et al. 2023

The Journal of Gene Medicine

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BackgroundCervical cancer (CC) remains a significant clinical challenge, even though its fatality rate has been declining in recent years. Particularly in developing countries, the prognosis for CC patients continues to be suboptimal despite numerous therapeutic advances.MethodsUsing The Cancer Genome Atlas database, we extracted CC‐related data. From this, 52 methylation‐related genes (MRGs) were identified, leading to the selection of a 10 long non‐coding RNA (lncRNA) signature co‐expressed with these MRGs. R programming was employed to filter out the methylation‐associated lncRNAs. Through univariate, least absolute shrinkage and selection operator (i.e. LASSO) and multivariate Cox regression analysis, an MRG‐associated lncRNA model was constructed. The established risk model was further assessed via the Kaplan–Meier method, principal component analysis, functional enrichment annotation and a nomogram. Furthermore, we explored the potential of this model with respect to guiding immune therapeutic interventions and predicting drug sensitivities.ResultsThe derived 10‐lncRNA signature, linked with MRGs, emerged as an independent prognostic factor. Segmenting patients based on their immunotherapy responses allowed for enhanced differentiation between patient subsets. Lastly, we highlighted potential compounds for distinguishing CC subtypes.ConclusionsThe risk model, associated with MRG‐linked lncRNA, holds promise in forecasting clinical outcomes and gauging the efficacy of immunotherapies for CC patients.

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Section: Discussionmentioning

confidence: 96%

“…A significant relationship between the risk‐score signature and immune cell infiltration was also found. Tumor formation and anti‐tumor immunity are strongly influenced by the TME, which encompasses a variety of immunological and stromal cell types 84 . MRGs and TME immune cell infiltration have been linked in previous stusies 72,85 .…”

Section: Discussionmentioning

confidence: 99%

An m1A/m6A/m5C‐associated long non‐coding RNA signature: Prognostic and immunotherapeutic insights into cervical cancer

Pan,

Lin,

Dai

et al. 2023

The Journal of Gene Medicine

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“…This variation can cause some individuals to develop resistance to radiation therapy ( 7 , 8 ). Consequently, a subset of patients with CC undergoing radiation therapy may fail to achieve effective local disease control, significantly impacting treatment efficacy and long-term prognosis ( 23 , 24 ). Current prognostic and risk assessment systems for CC do not incorporate an evaluation of radiotherapy sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

Wang,

Mou,

et al. 2024

Front. Endocrinol.

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BackgroundRadiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer.MethodsThe present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays.ResultsThis process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC.ConclusionTo summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

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“…For example, some tumor cells are shown to express programmed cell death ligand-1 (PD-L1), which binds to the programmed cell death protein 1 (PD-1) receptor on the surface of T cells and inhibits their activity ( 23 ). Meanwhile, expression of the HPV E6 and E7 oncogenes upregulates PD-L1 by suppressing p53 and Rb ( 24 , 25 ). The immunosuppressive microenvironment caused by HPV infection is a potential target for immunotherapy.…”

Section: Immunological Mechanism Of CCmentioning

confidence: 99%

Immune checkpoint blockade for locally advanced or recurrent/metastatic cervical cancer: An update on clinical data

Song

Zou

2022

Front. Oncol.

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Immunotherapy has shown great promise in the field of oncology, and recent clinical trials have illustrated that immune checkpoint blockade (ICB) is safe and effective at treating a range of tumor types. Cervical cancer (CC) is the fourth most common malignancy in women. However, first-line treatments for locally advanced cervical cancer (LACC) and recurrent/metastatic (R/M) CC have limited efficacy. Thus, it is necessary to explore new treatment approaches. The National Comprehensive Cancer Network (NCCN) currently recommends pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, as a first line therapy for individuals with R/M CC. This study reviews the progress of ICB therapy for LACC and R/M CC and describes the current status of the combination of ICB therapy and other therapeutic modalities, including radiotherapy, chemotherapy, targeted therapy, and other immunotherapies. The focus is placed on studies published since 2018 with the aim of highlighting novel CC-specific immunotherapeutic approaches and treatment targets.

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Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance

Cited by 9 publications

References 169 publications

An m1A/m6A/m5C‐associated long non‐coding RNA signature: Prognostic and immunotherapeutic insights into cervical cancer

An m1A/m6A/m5C‐associated long non‐coding RNA signature: Prognostic and immunotherapeutic insights into cervical cancer

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

Immune checkpoint blockade for locally advanced or recurrent/metastatic cervical cancer: An update on clinical data

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